Several series of experiments are planned in continuing research on two peptides, substance P and neurotensin, that were originally isolated and chemically defined in this laboratory as well as the peptides, substance K, which is coded for in the same gene as substance P. These peptides have widespread but selective distribution throughout the central and peripheral nervous system and several endocrine tissues suggesting that these peptides subserve multiple physiological roles. The proposed studies include: 1) elucidation of the role of neurotensin in the central regulation of LH release; 2) endocrine regulation of SP and SK gene expression in the anterior pituitary and selected neural tissues during development as well as the distribution and function of SP in the anterior pituitary; and, 3) purification and biochemical characterization of SP (and SK) receptors. Further understanding of the physiological role(s) of substance P and NT in the hypothalamus and anterior pituitary should contribute to our understanding of the functions regulated by these structures. Understanding hormonal effects on the regulation of peptide gene expression during development should provide important insights into how neural and hormonal peptides respond to changes in endocrine milieu during maturation. The isolation and chemical characterization of the SP (and SK) receptor will provide a major step towards understanding processes regulated by these peptide- receptor interactions. Since SP (and SK) play important roles, for example, in the transmission of painful stimuli, the chemical definition of the active binding site of these peptides may lead to the development of new therapeutic approaches.